The intricate dynamics of local liquid-gas interactions in agitated bioreactors poses a difficulty in understanding the mechanistic relationships among critical operational design parameters and cellular growth, especially for large-scale pharmaceutical production. Traditional computer models have advanced the understanding of such complex interactions. Their implementation is, however, associated with considerable computational costs, power and wall-clock time, to effectively simulate dynamic multiphase phenomena existing within bioreactors. This study explores a novel modeling approach that leverages high-resolution Large Eddy Simulation (LES) and the Lattice Boltzmann Method (LBM) to simulate turbulent flows within an industrial bioreactor. This approach allows the practical simulation of millions of bubbles modeled individually in a computationally accelerated manner. The model performance was evaluated with the experimental data obtained at various working volumes, aeration and agitation conditions. A further comparison with a conventional Reynolds-averaged Navier–Stokes method also provided comparable results. Furthermore, to complement the root-cause analysis conducted experimentally, a detailed model was developed to comprehend the underlying mechanisms for cell death, incorporating changes in individual bubble sizes due to various mass exchanges, fluid-gas forces and hydrodynamic pressure. Additionally, the model provided in-depth insights into other technical considerations for a proposed change in the sparger design at elevated gassing flow rates, including oxygen transfer rate, bubble breakup rate and impeller flooding transitions.